PB2552: VAYHIA: A RANDOMIZED, DOUBLE-BLIND, PHASE III TRIAL TO ASSESS THE EFFICACY AND SAFETY OF IANALUMAB VS PLACEBO IN PATIENTS WITH WARM AUTOIMMUNE HEMOLYTIC ANEMIA THAT FAILED ≥1 LINE OF TREATMENT
Authors: Wilma Barcellini, Marc Michel, Adam Cuker, Nichola Cooper, Waleed Ghanima, Raymond Wong, Francesco Zaja, Fengkui Zhang, Vladimir Bezlyak, Thu Thuy Nguyen, Hanny Al-Samkari
Journal: HemaSphere (2023)

Topic: 28. Enzymopathies, membranopathies and other anemias Background: Autoimmune hemolytic anemias (AIHAs) are rare and heterogeneous disorders characterized by autoantibody destruction of red blood cells (RBCs). The most common form of AIHA is warm AIHA (wAIHA), which can occur without a known etiology (primary wAIHA) or because of an underlying condition (secondary wAIHA). Autoreactive B cells play a role in the pathophysiology of wAIHA by producing immunoglobulin G (IgG) autoantibodies that bind and lyse RBCs at body temperature, with or without complement involvement. Except for azathioprine, which is approved in some countries for second-line treatment (although rarely used), there are currently no other approved treatments for wAIHA. Corticosteroids and the anti-CD20 monoclonal antibody (mAb) rituximab are established off-label treatments for wAIHA but rarely achieve a long-term response after completion and may be associated with negative safety profiles. As such, there remains an unmet need for effective therapies for wAIHA. One potential therapeutic target is the B-cell activating factor receptor (BAFF-R), which mediates the differentiation, proliferation and survival of B cells. Ianalumab is an IgG1 mAb with a novel dual mechanism of action that combines blockade of BAFF-R with direct lysis and depletion of B cells. Aims: The aim of VAYHIA is to assess the efficacy and safety of ianalumab compared with placebo in patients (pts) with wAIHA that has failed ≥1 lines of treatment (NCT05648968, EudraCT no. 2022-001773-31). Methods: VAYHIA is a double-blind, multicenter, three-arm study that aims to randomize 90 pts with wAIHA. Pts must be aged ≥18 years, have a baseline hemoglobin (Hb) concentration of <10 g/dL with anemia-related symptoms and primary or secondary wAIHA that had an insufficient response to, or relapse after, ≥1 lines of treatment. Exclusion criteria include wAIHA secondary to hematologic disease involving bone marrow and use of B-cell depleting therapy (eg rituximab) <12 weeks prior to randomization. Pts will be randomized in a 1:1:1 ratio to receive a high ianalumab dose, low ianalumab dose or placebo; supportive care is allowed in all treatment arms. Randomization will be stratified by prior exposure to rituximab. Ianalumab or placebo will be administered intravenously every 4 weeks before all pts enter a safety follow-up period. The primary efficacy endpoint is durable Hb response, defined as Hb ≥10 g/dL and an increase of ≥2 g/dL from baseline for ≥8 consecutive weeks between Week 9 and Week 25 in the absence of rescue or prohibited treatment. Pts who still have a durable Hb response at Week 25 will enter an additional efficacy follow-up period (Figure). An optional open-label crossover period will allow pts who receive placebo and do not achieve a durable Hb response the opportunity to receive high-dose ianalumab. The key secondary efficacy endpoint is the duration of the durable Hb response, defined as the time from the first Hb assessment showing durable response to the earliest of the following events: Hb <10 g/dL for ≥2 consecutive weekly assessments, the start of any rescue or prohibited treatment, or death. Other secondary endpoints include time to response, quality of response, need for rescue treatment, safety, pharmacokinetics of ianalumab and pt-reported outcomes.Results: At the time of writing, no pts have been randomized into the VAYHIA study. Summary/Conclusion: There is an unmet need for effective therapies for wAIHA. VAYHIA is being conducted in pts with primary or secondary wAIHA to investigate whether ianalumab induces a durable Hb response that is maintained beyond the treatment period. Keywords: Monoclonal antibody, BAFF, Phase III, Autoimmune hemolytic anemia (AIHA)